By Susan Maas
Shameem Syeda and Gunda Georg are developing a promising nonhormonal option.
A plant-based compound that turns sperm into slowpokes may be the key to male birth control that’s effective and reversible with minimal side effects, three University of Minnesota researchers believe.
Gunda Georg, professor of medicinal chemistry and director of the U’s Institute for Therapeutics Discovery and Development, and Shameem Syeda, principal scientist at the ITDD, may have an edge on other researchers developing oral contraceptives for men: Their compound is nonhormonal, so it shouldn’t cause the weight gain, libido changes, and potential cardiovascular risks associated with hormonal pills.
For decades, different versions of a male hormonal birth control pill have come and gone without making it to market because they’ve shown “a number of drawbacks,” Georg says. Her team started working on nonhormonal approaches 15 years ago, after the National Institutes of Health put out a call for proposals. “They saw that it’s maybe not a good idea to put all your eggs in one basket,” she says, pun intended. “We don’t touch testosterone.”
Syeda and Georg’s most advanced project revolves around a toxic substance produced by African plants that’s historically been used for poison arrows. Unaltered, the extract, ouabain, is known to disrupt heart function by interfering with the proteins that transport sodium and potassium ions through cell membranes. But it also thwarts a transporter protein found in mature sperm cells.
Together with colleague Jon Hawkinson, research professor of medicinal chemistry and ITDD associate program director, Syeda and Georg devised a ouabain derivative that doesn’t affect the heart. “We took ouabain as a starting point and created a molecule, using chemical modifications, that’s a very selective, potent molecule,” Syeda explains. The result: inhibited sperm “motility.”
In other words, fast-swimming sperm are rendered listless and ineffectual. “With this approach, sperm are turning sluggish,” Georg says. And based on what they’ve seen in rat models, the change doesn’t impact sperm produced later. “We’ve seen some evidence that it would be reversible; it works only on the mature sperm,” Syeda adds. “Once treatment is stopped, it doesn’t show any effect on the new sperm.”
Georg doesn’t anticipate long-term effects. “It’s not affecting sperm development, it’s not interfering with cell division or any processes related to DNA,” she says. “It just affects motility as far as we know.”
A recent clinical finding in China affirms the U team’s line of inquiry. It turns out ouabain is naturally produced in small amounts in humans—and “men who have elevated endogenous ouabain are infertile compared to men who have normal levels,” Georg says.
The team’s next step is to conduct rat “mating trials” that they hope will be funded by the NIH. “Then we need to establish that fertility comes back, and that the rats’ [postcontraceptive] offspring are healthy—and that there are no potential toxicities,” Georg says. “If we’re lucky, we could be doing a clinical trial in five years.” Shortly after the U study was published in the March 8 Journal of Medicinal Chemistry, another male contraceptive made headlines as University of Washington and UCLA researchers moved forward on a hormonal birth control pill, called dimethandrolone undecanoate, that temporarily suppresses testosterone and two other hormones required for fertility. That iteration of hormonal birth control seems to show significantly reduced side effects, but any adverse consequences have been deal-killers for male contraceptives in the past. That, despite the fact that for decades, women have put up with the downsides of oral contraceptives.
Sharing contraceptive responsibility
In part, women have been more willing than men to tolerate oral contraceptive risks because pregnancy and childbirth also carry potential health impacts. But, with better male contraceptives on the horizon and changing cultural norms in many countries, the era of male birth control may finally be arriving. “People are changing, they’re more accepting,” Syeda says. “In India, for instance, older generations maintain that contraception is [only] for women, not men. But when we look at the younger generation, they are not thinking that way. They want to share the responsibility.”
Georg agrees, and believes consumer demand will drive interest from pharmaceutical companies, which thus far have shown less-than-enthusiastic support for male oral contraceptive research. “I think there’s going to be dialogue about it; I’m quite convinced that this will be accepted,” Georg says. “Obviously not by everybody, because not everyone accepts contraception in general.
“We’ve gotten many emails from men saying ‘when you start the clinical trial, I’m ready.’ And as more men take it up, the interest will grow. We want to expand opportunities for people to decide whether and when they want to start families.”
Susan Maas is a Minneapolis-based writer and editor. She is also Minnesota Alumni’s longtime copy editor.
Photo by Leila Navidi/©2018 Star Tribune
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